A nuclear factor that binds to ras-responsive enhancer elements is present in human tumor cells.
The ras protein can be viewed as molecular switches for undetermined signal transduction pathways. We are interested in defining the downstream effectors and targets associated with ras signal transduction. A nuclear target of ras action is the conserved sequence element TGACTCT, which functions as a ras-responsive transcriptional element (RRE). An Mr 120,000 nuclear factor present in transformed murine cells recognizes the RRE. Mutation of the conserved RRE element to the palindromic element AGACTCT created a binding site that is recognized with 5-fold greater affinity by the Mr 120,000 factor. The palindromic element functions as an RRE as determined by transient transfection assays. UV-crosslinking of nuclear factors in human tumor cell lines to the palindromic element revealed that an Mr 120,000 factor that recognized RREs was present in cells that contain activated Ha- or N-ras genes, but not in human tumor cells that lack activated ras. Expression of exogenous activated ras in a human tumor cell line that lacks the oncogene induced the Mr 120,000 factor. The Mr 120,000 factor, which we have termed ras-responsive factor 1, is an intermediate in the signal transduction pathway that links ras to the nucleus and may play a role in the initiation or progression of human tumors containing an activated ras gene.
Owen
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RD
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Ostrowski
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MC
D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000032:analysis*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D008156:Luciferases